Levodopa Reverses Cytokine-Induced Reductions in Striatal Dopamine Release

• Type of Material: Article
• Authors: Jennifer Felger, Emory University; Carla A. Hernandez, Emory University; Andrew H Miller, Emory University
• Language: English
• Date: 2015-02-01
• Publisher: Oxford University Press (OUP): Policy C - Option B
• Publication Version: Final Published Version
• Copyright Statement: © The Author 2015. Published by Oxford University Press on behalf of CINP.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1093/ijnp/pyu084
• Title of Journal or Parent Work: International Journal of Neuropsychopharmacology
• ISSN: 1461-1457
• Volume: 18
• Issue: 4
• Start Page: pyu084
• End Page: pyu084
• Grant/Funding Information: This work was supported by funds from the National Institute of Mental Health (R01MH083746;, K05MH069124;, and T32MH020018; to A.H.M. and F32MH093054 to J.C.F.) and by the National Center for Advancing Translational Sciences of the National Institutes of Health under award numbers UL1TR000454; and KL2TR000455.
• Keywords: Psychiatry; anhedonia; Neurosciences; dopamine; TRIAL; FATIGUE; PHASE-III; NITRIC-OXIDE; Science & Technology; BASAL GANGLIA; Pharmacology & Pharmacy; DOUBLE-BLIND; DEPRESSION; Life Sciences & Biomedicine; in vivo microdialysis; INTERFERON-ALPHA; RHESUS-MONKEYS; Neurosciences & Neurology; METHYLPHENIDATE; Clinical Neurology; cytokines; depression
• Research Categories: Psychology, Behavioral; Health Sciences, Oncology

Abstract

METHODS: Herein, we examined whether reduced striatal dopamine release in rhesus monkeys chronically treated with interferon-alpha can be restored by administration of the dopamine precursor levodopa via reverse in vivo microdialysis. RESULTS: Levodopa completely reversed interferon-alpha-induced reductions in striatal dopamine release. No changes were found in the 3,4-dihydroxyphenylacetic acid to dopamine ratio, which increases when unpackaged dopamine is metabolized via monoamine oxidase. BACKGROUND: Studies using neuroimaging and in vivo microdialysis in humans and nonhuman primates indicate that inflammatory cytokines such as interferon-alpha reduce dopamine release in the ventral striatum in association with depressive symptoms including anhedonia and psychomotor slowing. CONCLUSIONS: These findings suggest that inflammatory cytokines reduce the availability of dopamine precursors without affecting end-product synthesis or vesicular packaging and/or release and provide the foundation for future studies investigating therapeutic strategies that facilitate availability of dopamine precursors to improve depressive symptoms in patient populations with increased inflammation.